GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options, underscoring the need for novel therapeutic targets. Metabolic reprogramming is a hallmark of PDAC, enabling tumor cells to sustain rapid proliferation and survive under nutrient-deprived conditions. Whil...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Molecular & Cellular Oncology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/23723556.2025.2518773 |
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| author | Jenna N. Duttenhefner Katie M. Reindl |
| author_facet | Jenna N. Duttenhefner Katie M. Reindl |
| author_sort | Jenna N. Duttenhefner |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options, underscoring the need for novel therapeutic targets. Metabolic reprogramming is a hallmark of PDAC, enabling tumor cells to sustain rapid proliferation and survive under nutrient-deprived conditions. While glutathione S-transferase pi 1 (GSTP1) is a known regulator of redox homeostasis in PDAC, its role in metabolic adaptation remains unclear. Here, we show that GSTP1 knockdown disrupts PDAC metabolism, leading to downregulation of key metabolic enzymes (ALDH7A1, CPT1A, SLC2A3, PGM1), ATP depletion, mitochondrial dysfunction, and phospholipid remodeling. Phospholipid remodeling, including an increase in phosphatidylcholine (PC) levels, further suggests a compensatory response to metabolic stress. Importantly, GSTP1 knockdown led to elevated lipid peroxidation, increasing 4-hydroxynonenal (4-HNE) accumulation. Treatment with the antioxidant N-acetyl cysteine (NAC) partially restored metabolic gene expression, reinforcing GSTP1’s role in the interplay between redox regulation and metabolism in PDAC. By disrupting multiple metabolic pathways, GSTP1 depletion creates potential therapeutic vulnerabilities that could be targeted through metabolic and oxidative stress-inducing therapies to enhance treatment efficacy. |
| format | Article |
| id | doaj-art-ccca6a6575e44c43abb3a56cf59c5ae9 |
| institution | Kabale University |
| issn | 2372-3556 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Molecular & Cellular Oncology |
| spelling | doaj-art-ccca6a6575e44c43abb3a56cf59c5ae92025-08-20T03:45:31ZengTaylor & Francis GroupMolecular & Cellular Oncology2372-35562025-12-0112110.1080/23723556.2025.2518773GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cellsJenna N. Duttenhefner0Katie M. Reindl1Department of Biological Sciences, North Dakota State University, Fargo, ND, USADepartment of Biological Sciences, North Dakota State University, Fargo, ND, USAPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options, underscoring the need for novel therapeutic targets. Metabolic reprogramming is a hallmark of PDAC, enabling tumor cells to sustain rapid proliferation and survive under nutrient-deprived conditions. While glutathione S-transferase pi 1 (GSTP1) is a known regulator of redox homeostasis in PDAC, its role in metabolic adaptation remains unclear. Here, we show that GSTP1 knockdown disrupts PDAC metabolism, leading to downregulation of key metabolic enzymes (ALDH7A1, CPT1A, SLC2A3, PGM1), ATP depletion, mitochondrial dysfunction, and phospholipid remodeling. Phospholipid remodeling, including an increase in phosphatidylcholine (PC) levels, further suggests a compensatory response to metabolic stress. Importantly, GSTP1 knockdown led to elevated lipid peroxidation, increasing 4-hydroxynonenal (4-HNE) accumulation. Treatment with the antioxidant N-acetyl cysteine (NAC) partially restored metabolic gene expression, reinforcing GSTP1’s role in the interplay between redox regulation and metabolism in PDAC. By disrupting multiple metabolic pathways, GSTP1 depletion creates potential therapeutic vulnerabilities that could be targeted through metabolic and oxidative stress-inducing therapies to enhance treatment efficacy.https://www.tandfonline.com/doi/10.1080/23723556.2025.2518773Pancreatic ductal adenocarcinomaglutathione S-transferase pi 1 (GSTP1)metabolic reprogrammingmetabolomicstherapeutic targeting |
| spellingShingle | Jenna N. Duttenhefner Katie M. Reindl GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells Molecular & Cellular Oncology Pancreatic ductal adenocarcinoma glutathione S-transferase pi 1 (GSTP1) metabolic reprogramming metabolomics therapeutic targeting |
| title | GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells |
| title_full | GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells |
| title_fullStr | GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells |
| title_full_unstemmed | GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells |
| title_short | GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells |
| title_sort | gstp1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells |
| topic | Pancreatic ductal adenocarcinoma glutathione S-transferase pi 1 (GSTP1) metabolic reprogramming metabolomics therapeutic targeting |
| url | https://www.tandfonline.com/doi/10.1080/23723556.2025.2518773 |
| work_keys_str_mv | AT jennanduttenhefner gstp1knockdowninducesmetabolicchangesaffectingenergyproductionandlipidbalanceinpancreaticcancercells AT katiemreindl gstp1knockdowninducesmetabolicchangesaffectingenergyproductionandlipidbalanceinpancreaticcancercells |